The problem of alcoholism in American Indians has been comprehensively addressed in three family linkage datasets: 1] SW tribe; 2] Eastern Oklahoma tribe with low prevalence of alcoholism - field study in progress directed by Dr. Long; 3] Plains Indian tribe with neuropsychological data [EEG] - analytical studies in progress; and also in a large cross-population study in progress - the Ten Tribes Study which systematically compares 300 randomly sampled subjects from each tribe. In addition, LNG is the genetics collaborating laboratory on the first pharmacogenetic study on alcoholism treatment response [to naltrexone and sertraline]. This study, on Alaska Natives, is led by S. O'Malley. The whole genome scan for the SW tribe detected two potential new loci for alcoholism: the DRD4 region at the chromosome 11p telomere, and the region of the GABAA cluster near the chromosome 4p centromere. The SW Indian sample is a large family (N=582) comprising a sizeable fraction of a Southwestern tribe with a high rate of alcoholism (85% of males, greater than 50% of females). This family was systematically interviewed, substantial evidence for familial transmission of alcoholism was found, and then it was evaluated for genetic linkage in collaboration with investigators from NIDDK (W. Knowler, R. Hanson, P. Bennett) and, using a large (N=517) panel of DNA markers which covered all human chromosomes except the sex chromosomes: X and Y. The SW tribe studies were informative for the meaning and consequences of alcohol-related diagnoses in American Indians. The results are representative because 1] the very large family was ascertained solely on the basis of structure and availability, 2] the family is representative of the tribe in coefficient of relationship and demography, and 3] CAGE scores do not differ from a random sample of 3112 individuals studied collaboratively by NIDDK [Hanson et al]. The evidence from the SW tribe is that binge drinking is neither benign nor beneficial, that alcoholism is familial, and that the same patterns of psychiatric comorbidity seen in the general U.S. population [National Comorbidity Survey] are seen in Indian alcoholics. Almost all of the large fraction of the population who were binge drinkers were also alcoholics, and binge drinkers tended to become alcoholic at a younger age. Regardless of whether binge drinkers met criteria for alcoholism, they were dramatically worse off in each of the four symptom categories evaluated in the SADS-L: social, work, violence/lawlessness and physical. We found the same heavy clusterings of psychiatric disorders with alcoholism as previously observed in the general population of the U.S. These results may help lay to rest the misconception that drinking, particularly binge drinking, is other than deleterious to American Indians and regardless of whether binge drinking is culturally determined or congruent.